1. Field of the Invention
The present invention relates to DNA molecules that encode lysine 2,3-aminomutase. More particularly, this invention relates to the use of recombinant host cells comprising such DNA molecules to produce pure L-.beta.-lysine.
2. Related Art
Although less abundant than the corresponding .alpha.-amino acids, .beta.-amino acids occur in nature in both free forms and in peptides. Cardillo and Tomasini, Chem. Soc. Rev. 25:77 (1996); Sewald, Amino Acids 11:397 (1996). Since .beta.-amino acids are stronger bases and weaker acids than .alpha.-amino acid counterparts, peptides that contain a .beta.-amino acid in place of an .alpha.-amino acid, have a different skeleton atom pattern, resulting in new properties. For example, various peptides are protease inhibitors because the presence of the .beta.-amino-.alpha.-hydroxy acid motif acts as a transition state mimic of peptide hydrolysis.
.beta.-Amino acids are of particular interest in the preparation of medicaments, such as .beta.-lactams. Well-known .beta.-lactam antimicrobial agents include penicillins, cephalosporins, carbapenems, and monobactams. Other examples of medically useful molecules that contain .beta.-amino-.alpha.-hydroxy acids include the anti-tumor agent taxol, the anti-bacterial agent, dideoxykanamicin A, bestatin, an immunological response modifier, the kynostatins, which are highly potent human immunodeficiency virus-1 protease inhibitors, and microginin, a tetrapeptide which has anti-hypertensive properties. Accordingly, enantiomerically pure .beta.-amino-.alpha.-hydroxy acids are of considerable importance as crucial components of pharmacologically active compounds.
In the 1950's, L-.beta.-lysine was identified in several strongly basic peptide antibiotics produced by Streptomyces. Antibiotics that yield L-.beta.-lysine upon hydrolysis include viomycin, streptolin A, streptothricin, roseothricin and geomycin. Stadtman, Adv. Enzymol. Relat. Areas Molec. Biol. 38:413 (1973). .beta.-Lysine is also a constituent of antibiotics produced by the fungi Nocardia, such as mycomycin, and .beta.-lysine may be used to prepare other biologically active compounds. However, the chemical synthesis of .beta.-lysine is time consuming, requires expensive starting materials, and results in a racemic mixture.
Therefore, a need exists for an improved method of preparing enantiomerically pure .beta.-amino acids, such as .beta.-lysine.